Contribution To Literature:

The ORBITA trial showed that among patients with stable angina, PCI does not result in greater improvements in exercise times or anginal frequency compared with a sham procedure, despite the presence of anatomically and functionally significant stenoses.

Description:

The goal of the trial was to assess the efficacy of percutaneous coronary intervention (PCI) compared with a sham placebo procedure for angina relief among patients with stable angina.

Study Design

Patients with stable angina and evidence of severe single-vessel stenosis were randomized in a 1:1 fashion to either PCI or a placebo sham procedure. After enrollment, patients received 6 weeks of medication optimization. Coronary angiography was done via a radial or femoral arterial approach with auditory isolation achieved by placing over-the-ear headphones playing music on the patient throughout the procedure. In all patients, a research invasive physiological assessment of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) was done. The operator was blinded to the physiology values and therefore did not use them to guide treatment. Randomization occurred after this physiological assessment.

For patients allocated to PCI, the clinical operator used drug-eluting stents (DES) to treat all lesions that were deemed to be angiographically significant, with a mandate to achieve angiographic complete revascularization. After PCI, iFR and FFR were measured again. In the placebo group, patients were kept sedated for at least 15 minutes on the catheter laboratory table and the coronary catheters were withdrawn with no intervention having been done.

Total number of enrollees: 200

Duration of follow-up: 6 weeks

Mean patient age: 66 years

Percentage female: 27%

Inclusion criteria:

Age 18-85 years

Stable angina/angina equivalent

At least one angiographically significant lesion (≥70%) in a single vessel that was clinically appropriate for PCI

Compared with placebo, PCI improved stress echocardiography by 1.07 segment units (p < 0.00001). There was a significant interaction with both FFR and iFR values, with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction < 0.00001 for both). There was no interaction between angina relief with PCI vs. placebo and FFR/iFR values.

Interpretation:

The results of this trial indicate that among patients with stable angina, PCI does not result in greater improvements in exercise times or anginal frequency compared with a sham procedure. This was despite the presence of anatomically and functionally significant stenoses. PCI did however resolve ischemia more effectively, as ascertained by follow-up stress echocardiography.

This is clearly a landmark trial, but several issues need to be considered. The trial was extremely well done, with careful assessments of ischemia pre- and post-procedure, and appropriate use of antianginal medications. Although powered for exercise treadmill-based endpoints, the trial appears to be too small to address a question of this magnitude. The COURAGE trial, for instance, enrolled 2,300 patients with stable angina. Moreover, changes in Duke treadmill score and exercise time were both numerically higher in the PCI arm, and it is unknown if a larger sample size would have detected more modest improvements in exercise capacity.

Accordingly, these findings need to be validated in a larger randomized controlled trial. This trial also highlights the value of sham controls for procedure-oriented trials, where a procedural placebo effect is balanced out. A similar benefit of using sham controls was noted in the SYMPLICITY HTN-3 trial earlier.